Dynamic kinetic resolution of α-chloro β-keto esters and phosphonates: hemisynthesis of Taxotere® through Ru-DIFLUORPHOS asymmetric hydrogenation

The dynamic kinetic resolution (DKR) of racemic alpha-chloro beta-ketoesters and alpha-chloro beta-ketophosphonates through ruthenium-mediated asymmetric hydrogenation is reported. The corresponding alpha-chloro beta-hydroxyesters and alpha-chloro beta-hydroxyphosphonates were obtained in good to high enantio- and diastereomeric excesses using, in particular, the atropisomeric ligand DIFLUORPHOS. This methodology allowed an efficient preparation of the anti phenylisoserine side chain of Taxotere (R) which has been used for the hemisynthesis of the cancer therapeutic agent itself. In addition, C-13 NMR in chiral oriented solvents was used to investigate the DKR effect. (C) 2010 Elsevier Ltd. All rights reserved.